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  1. Article ; Online: Good Outcomes in Salvage Therapy of Fusariosis in Patients With Leukemia: Is It the Host or the Drug?

    Matsuo, Takahiro / Wurster, Sebastian / Kontoyiannis, Dimitrios P

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2024  

    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciad768
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    Zs.A 1505: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Zs.MO 480: Show issues

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  2. Article: Adjunct Terbinafine in Patients With Leukemia and Invasive Fusariosis With Skin Lesions: Discordance Between Responses of Skin Lesions and Systemic Outcomes.

    Matsuo, Takahiro / Wurster, Sebastian / Jiang, Ying / Tarrand, Jeffrey / Kontoyiannis, Dimitrios P

    Open forum infectious diseases

    2024  Volume 11, Issue 2, Page(s) ofae068

    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofae068
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  3. Article ; Online: Drosophila melanogaster as a Rapid and Reliable In Vivo Infection Model to Study the Emerging Yeast Pathogen Candida auris.

    Wurster, Sebastian / Albert, Nathaniel D / Kontoyiannis, Dimitrios P

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2517, Page(s) 299–316

    Abstract: While mammalian models remain the gold standard to study invasive mycoses, mini-host invertebrate models have provided complementary platforms for explorative investigations of fungal pathogenesis, host-pathogen interplay, and antifungal therapy. ... ...

    Abstract While mammalian models remain the gold standard to study invasive mycoses, mini-host invertebrate models have provided complementary platforms for explorative investigations of fungal pathogenesis, host-pathogen interplay, and antifungal therapy. Specifically, our group has established Toll-deficient Drosophila melanogaster flies as a facile and cost-effective model organism to study candidiasis, and we have recently expanded these studies to the emerging and frequently multidrug-resistant yeast pathogen Candida auris. Our proof-of-concept data suggest that fruit flies could hold a great promise for large-scale applications in antifungal drug discovery and the screening of C. auris (mutant) libraries with disparate pathogenic capacity. This chapter discusses the advantages and limitations of D. melanogaster to study C. auris candidiasis and provides a step-by-step guide for establishing and troubleshooting C. auris infection and antifungal treatment of Toll-deficient flies along with essential downstream readouts.
    MeSH term(s) Animals ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Candida ; Candida auris ; Candidiasis/drug therapy ; Candidiasis/microbiology ; Drosophila melanogaster/microbiology ; Mammals ; Microbial Sensitivity Tests ; Saccharomyces cerevisiae
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2022-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2417-3_24
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  4. Article ; Online: Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions.

    Wurster, Sebastian / Watowich, Stephanie S / Kontoyiannis, Dimitrios P

    Frontiers in immunology

    2022  Volume 13, Page(s) 1018202

    Abstract: Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through ... ...

    Abstract Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a "sweet spot" for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.
    MeSH term(s) Animals ; Antifungal Agents/therapeutic use ; Immunotherapy ; Immunologic Factors/therapeutic use ; Neoplasms/drug therapy ; Neoplasms/pathology ; Mycoses/drug therapy ; Tumor Microenvironment
    Chemical Substances Antifungal Agents ; Immunologic Factors
    Language English
    Publishing date 2022-10-25
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1018202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Candida auris Bloodstream Infection Induces Upregulation of the PD-1/PD-L1 Immune Checkpoint Pathway in an Immunocompetent Mouse Model.

    Wurster, Sebastian / Albert, Nathaniel D / Kontoyiannis, Dimitrios P

    mSphere

    2022  Volume 7, Issue 2, Page(s) e0081721

    Abstract: Candida auris is a globally spreading yeast pathogen causing bloodstream infections with high mortality in critically ill patients. The inherent antifungal drug resistance of most C. auris isolates and threat of multidrug-resistant strains create a need ... ...

    Abstract Candida auris is a globally spreading yeast pathogen causing bloodstream infections with high mortality in critically ill patients. The inherent antifungal drug resistance of most C. auris isolates and threat of multidrug-resistant strains create a need for adjunct immunotherapeutic strategies. While C. albicans candidemia was shown to induce immune paralysis and activation of inhibitory immune checkpoints,
    MeSH term(s) Animals ; B7-H1 Antigen/genetics ; B7-H1 Antigen/therapeutic use ; Candida/genetics ; Candida albicans ; Candida auris ; Candidemia/drug therapy ; Candidiasis, Invasive ; Disease Models, Animal ; Humans ; Immune Checkpoint Proteins ; Mammals ; Mice ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/therapeutic use ; Up-Regulation
    Chemical Substances B7-H1 Antigen ; Immune Checkpoint Proteins ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2022-02-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/msphere.00817-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Thesis ; Online: Modellierung, Simulation und Charakterisierung des Abbrandes extrudierbarer Festtreibstoffe mit komplexer Querschnittgeometrie

    Wurster, Sebastian

    2018  

    Abstract: Die vorliegende Arbeit leistet einen Beitrag zur Modellierung und Simulation des Abbrandes extrudierbarer Festtreibstoffe mit komplexer Querschnittgeometrie sowie allgemein zur Abbrandcharakterisierung von Festtreibstoffen. Dazu wird die ... ...

    Abstract Die vorliegende Arbeit leistet einen Beitrag zur Modellierung und Simulation des Abbrandes extrudierbarer Festtreibstoffe mit komplexer Querschnittgeometrie sowie allgemein zur Abbrandcharakterisierung von Festtreibstoffen. Dazu wird die Geometrieänderung der Querschnittgeometrie während des Abbrandes durch einen gitterbasierten Algorithmus modelliert. Dieser basiert auf zellulären Automaten und wird als ICT-Cellular-Combustion-Algorithm bezeichnet. Dieser wird mit Algorithmen zur Präprozessierung der Eingabegeometrien und einem thermodynamischen Modell für den Druckaufbau in einer ballistischen Bombe kombiniert. Das entwickelte Modell ermöglicht die numerische Simulation der Geometrieänderung von extrudierbaren Festtreibstoffen während des gesamten Verbrennungsprozesses für nahezu beliebige Querschnittgeometrien. Mit Hilfe des Modells und experimentellen Messdaten kann eine Zielfunktion konstruiert und durch numerische Optimierungsalgorithmen minimiert werden. Dies ermöglicht die experimentelle Bestimmung der druckabhängigen Regressionsgeschwindigkeit der Abbrandoberfläche mit hoher Genauigkeit auch für geometrisch komplexe Festtreibstoffe unter gleichzeitiger Verwendung kleiner Probenmengen.
    Keywords material science ; testing of materials ; Festtreibstoff ; Abbrandcharakterisierung ; Abbrandsimulation ; Formfunktion ; ICT-Cellular-Combustion-Algorithm ; Physiker ; Ingenieur ; 660
    Subject code 600
    Language German
    Publisher Fraunhofer Verlag
    Publishing country de
    Document type Thesis ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Evaluation of the James Initiation Criterion in the 21mm and 50mm PMMA Gap Test

    Wurster, Sebastian

    2017  

    Abstract: S.749-753 ... The gap test has been used for several decades as a measure for the shock sensitivity of high explosives. Normally the axial pressure in the gap is used as the necessary initiation pressure of a high explosive for a shock to detonation ... ...

    Abstract S.749-753

    The gap test has been used for several decades as a measure for the shock sensitivity of high explosives. Normally the axial pressure in the gap is used as the necessary initiation pressure of a high explosive for a shock to detonation transition. But it has been shown in the past that the pressure in the gap is not a suitable measure for shock sensitivity and other criteria like the James criterion in terms of critical energy fluence and critical specific kinetic energy should be used. To evaluate the James criterion in the 21mm and 50mm polymethylmethacrylate (PMMA) gap test numerical simulations are conducted. To validate the simulations a 21mm water gap test is simulated and compared to experimental results, where the axial pressure calibration can be reproduced with high accuracy. With the results from the simulation of the 21mm and 50mm gap test it is shown that at the same maximum axial pressure the energy fluence is higher in the 50mm gap test. This explains to some extent the higher initiation pressures observed in smaller gap tests. The James criterion is derived and it is shown that the two gap tests probe very different regions in the energy fluence vs. specific kinetic energy plane. The results can be used as a calibration for the gap tests and are intended to improve the comparability of gap test results among each other and with different initiation experiments like flyer or heavy fragment impact testing.

    42

    Nr.7
    Keywords energy fluence ; gap test ; Initiation Criteria ; simulation ; 660 ; 662
    Subject code 621
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Invasive fusariosis in patients with leukaemia in the era of mould-active azoles: increasing incidence, frequent breakthrough infections and lack of improved outcomes.

    Matsuo, Takahiro / Wurster, Sebastian / Jiang, Ying / Sasaki, Koji / Tarrand, Jeffrey / Lewis, Russell E / Kontoyiannis, Dimitrios P

    The Journal of antimicrobial chemotherapy

    2024  Volume 79, Issue 2, Page(s) 297–306

    Abstract: Objectives: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are ... ...

    Abstract Objectives: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients.
    Methods: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis.
    Results: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04).
    Conclusions: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.
    MeSH term(s) Adult ; Humans ; Fusariosis/drug therapy ; Fusariosis/epidemiology ; Antifungal Agents/therapeutic use ; Breakthrough Infections ; Azoles ; Incidence ; Retrospective Studies ; Triazoles ; Fungi ; Leukemia/complications ; Leukemia/epidemiology ; Leukemia/drug therapy ; Neutropenia/complications ; Neutropenia/drug therapy
    Chemical Substances Antifungal Agents ; Azoles ; Triazoles
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkad377
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    Zs.A 1197: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Zs.MO 124: Show issues

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  9. Article ; Online: Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis.

    Egge, Stephanie L / Wurster, Sebastian / Cho, Sung-Yeon / Jiang, Ying / Axell-House, Dierdre B / Miller, William R / Kontoyiannis, Dimitrios P

    Journal of fungi (Basel, Switzerland)

    2024  Volume 10, Issue 1

    Abstract: Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable ... ...

    Abstract Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from 2000-2020. Seventeen out of sixty-three reviewed patients (27.0%) had sinopulmonary co-occurrence of GNRs (most commonly
    Language English
    Publishing date 2024-01-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2784229-0
    ISSN 2309-608X ; 2309-608X
    ISSN (online) 2309-608X
    ISSN 2309-608X
    DOI 10.3390/jof10010041
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  10. Conference proceedings: Literatur-Review: Wirt-Pathogen-Interaktion bei invasiven Mykosen

    Wurster, Sebastian

    2016  , Page(s) 16sac13

    Event/congress Frühjahrstagung der Sektion Antimykotische Chemotherapie 2016; Bonn; Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG); 2016
    Keywords Medizin, Gesundheit
    Publishing date 2016-04-20
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/16sac13
    Database German Medical Science

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